A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis

Inclusion Criteria:

1. Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent
Form (ICF).

2. A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation

3. Weight ≥ 40 kg.

4. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline

5. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender
and height at screening

Exclusion Criteria:

1. History of clinically meaningful unstable or uncontrolled chronic disease that makes
the subject unsuitable for inclusion in the study in the opinion of the investigator.

2. Unstable pulmonary status or respiratory tract infection requiring a change in therapy
within 4 weeks of baseline.

3. Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while
sleeping.

4. Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to
the first study drug administration.

5. History of hepatic cirrhosis with portal hypertension.

6. Abnormal liver function test at screening; defined as aspartate aminotransferase (AST)
and/or alanine aminotransferase (ALT) and/ or alkaline phosphatase and/or
gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN); and/or total
bilirubin (>1.5 times ULN)

7. Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula at
screening.